PROJECT SUMMARY All animals use sensory cues to find their way through complex environments and locate vital resources such as food or mates. From simple organisms such as worms finding nutrient-rich soil at centimeter-scale distances to polar bears following their noses across kilometers to feed upon seal carcasses, the ability to navigate an environment using odors is one of the most evolutionarily ancient and widespread examples of this complex behavior. Interest in the ability to navigate with odors has spanned decades and resulted in numerous models suggesting how animals can accomplish this feat. Testing these models is extremely difficult because in nearly all terrestrial environments odors are transported as fluctuating plumes by turbulent air flow. This necessitates either the use of simplifying models for odor flow or complex three-dimensional computational fluid dynamics simulations. In both cases, only statistical connections can be made between the performance of a simulated searcher and the behavior and neural processing of an animal. This limitation rules out the ability to combine moment-to-moment neural recordings with the sensory input guiding an animal?s behavior. This proposal represents a cross-disciplinary effort between experts in fluid dynamics, olfactory systems neuroscience, and neurophysiology to directly establish the algorithms used for odor-guided navigation and the neural implementation of these algorithms in the early olfactory system of mice. We will use newly developed, miniature odor sensors to record odor plumes at the mouse nose during odor-guided navigation. By combining these sensor readings with computational models of odor flow we will directly test the behavioral algorithms used by mice to navigate with odor plumes. To establish the neural implementation of these algorithms we will perform large-scale neural imaging and electrophysiology recordings from the early olfactory system while monitoring odor plume input at the nose. We will also use viral labeling techniques to selectively record neural activity from cells that send output to specific downstream cortical structures. By recording neural activity from olfactory bulb cells with specific cortical targets we will test how odor information is routed from sensory to decision-making areas to support odor-guided navigation. Finally, we will combine these levels of analysis to generate a complete model of odor-guided navigation that connects behavioral algorithms to neural implementation.